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Pink Sheet – Califf Sees Potential For New Emergency Use Authorities But Concerned About Industry Follow Through

Pink Sheet – Califf Sees Potential For New Emergency Use Authorities But Concerned About Industry Follow Through

US Food and Drug Administration Commissioner Robert Califf is willing to explore emergency use authorization use outside of COVID-19-like pandemic situations, but also is concerned about the drug industry’s lack of financial incentives to finish studying products given the expedited path to market.

Califf was asked about the potential for EUAs in areas like non-opioid pain medicine or certain cancer types as an incentive for innovation during the 13 February Prevision Policy/Friends of Cancer Research Biopharma Congress.

“I think there are all categories of things, you could say EUAs, you could say various means of accelerated approval,” Califf said. “I think there’s good reason to be creative in that arena, as long as we fill in the second part. And I think industry by and large has resisted doing a good job with the second part.”

“I wrote papers about this in my youth,” he added. “You do a net present value calculation, you’re almost always better relying on marketing and not relying on hardcore evidence. And we need to make it so the net present value calculation comes out positive for doing the right thing.”

The COVID-19 pandemic saw unprecedented use of the emergency use authorization pathway, which allows for a lower “may be effective,” determination by the FDA, making the once unknown authority into a household name. Sponsors must show the known and potential benefits of authorization outweigh the known and potential risks. The agency also must determine that there are no formally approved alternatives available, though the definition of available alternatives has been fairly flexible during COVID. (Also see “Novavax EUA Justified By US FDA With Claims Of COVID Vaccine Supply Constraints” – Pink Sheet, 14 Jul, 2022.)

Some close agency watchers predicted earlier in the pandemic that the FDA would face new pressure to use EUA-like authorities in other diseases areas, once the public became familiar with it. The FDA often is under intense political pressure to approve drugs faster and operates in an environment where the public’s tolerance for risk and unknowns is high when faced with serious, life-threatening conditions and little to no adequate treatment options. (Also see “Pandemic Perspectives: How COVID Emergency Use Authorizations Could Reshape US FDA” – Pink Sheet, 1 Apr, 2021.)

At the same time, the FDA and pharmaceutical industry have come under scrutiny in recent years for delayed or limited follow through on confirmatory trials when the agency exercises its regulatory flexibilities under programs like accelerated approval. Concerns have grown after patients were charged high costs for many of the treatments cleared through the pathway. (Also see “Medicare Will Test Payment Model For Accelerated Approvals To ‘Expedite’ Confirmatory Trials” – Pink Sheet, 14 Feb, 2023.)

Califf, unsurprisingly, is aware of both sentiments.

“There’s a pretty large tolerance in the regulatory system,” he said. “And I think the will – you know Americans like to take some risk in return for benefit – I think there’s a lot of interest publicly in this, but we can’t do it if people are just going to go out and sell the treatment for a billion dollars and never bring the evidence in a time frame that is reasonable.”

The commissioner said he was particularly interested in thinking about whether the FDA could apply an EUA-type authority to opioid alternatives, noting that the US has a formal public health emergency declaration for the opioid crisis. First enacted in October 2017 under the Trump administration, the emergency was last renewed in October 2022.

“What incentives would it take for the people with money to put money into” new treatments for pain that are not addictive? Califf asked. “I’m not saying I know the answer to that but it seems like a question we should be asking. We’re going to lose more people to overdoses next year than COVID,” if COVID continues on its current path, Califf said.

However, the opioid emergency declaration is different from the public health emergency determination necessary to allow emergency use authorizations. Congress likely would need to revise current law to make EUAs possible in the opioid alternative space.

Under section 564 of the Food, Drug and Cosmetic Act, the Health and Human Services Secretary can determine that the circumstances justify issuing EUAs if “there is a public health emergency or significant potential for a public health emergency that affects, or has significant potential to affect, national security or the health and security of U.S. citizens living abroad and involves a biological, chemical, radiological, or nuclear agent or disease or condition that may be attributable to such agent(s).”

“I think the key challenge is the language about ‘national security’ and also ‘biological, chemical, radiological, or nuclear agents,’” said Holly Fernandez Lynch, a bioethicist and lawyer at the University of Pennsylvania. “So it doesn’t have to be an infectious disease, per se (it could be the threat of radiation, for example), but there has to be some outside ‘agent,’ and I don’t see that for most diseases and conditions. So yes, it would require legislative change, I think.”

Still, there may be ways for the FDA to take EUA-like approaches without congressional authority, such as adapting communication strategies used for COVID to other disease areas. (Also see “Firms Hope To Adapt COVID Vaccine Trial Design, FDA Communication Approaches To Other Diseases” – Pink Sheet, 26 Apr, 2022.)

Califf said civil servants at FDA, not political appointees like a commissioner, are responsible for making most decisions about approval flexibilities.

“But I will surely be asking them questions about where’s the creativity in areas where there’s unmet need and industry is failing,” he said.

Tobacco cessation products, are another area that Califf thinks the drug industry should be investing more resources, given the 500,000 Americans who die from combustible tobacco-related diseases each year.

A stronger approach may be needed to get industry into these spaces, he added.

“I like sort of the combination of sticks and carrots, and you’ve got to wonder whether there’s some stick that can go with a carrot,” Califf said. “I do like positive incentives also, so I’m not saying just beat up on people. But we’re going to lose a lot of people. There’s not much coming from industry to help out. It can’t always be the case that you give people a gazillion dollars to get something done.”